Plasma amitriptyline level after acute administration, and driving performance in healthy volunteers.
OBJECTIVE
Amitriptyline triggers the impairment of cognitive and motor functions and has been confirmed to have harmful effects on driving performance. Although interindividual differences in plasma concentration may cause variations in driving performance, the relationship between plasma amitriptyline concentration and its effect on driving performance has not been completely elucidated. Thus, the aim of the present study was to assess the influence of individual pharmacokinetic differences on driving performance and cognitive functions.


METHODS
In this double-blinded study, 17 healthy male volunteers were given an acute, single, 25-mg dose of amitriptyline. The subjects were assigned three driving simulator tasks, three cognitive tasks, and the questionnaire of the Stanford Sleepiness Scale at the baseline and at 4 h after dosing. The plasma amitriptyline concentrations were measured on high-performance liquid chromatography.


RESULTS
A significant positive correlation was observed between the plasma amitriptyline concentration and road-tracking performance (r = 0.543, P < 0.05). There was no significant correlation between the plasma amitriptyline concentration and other driving performance, cognitive functions, and subjective somnolence.


CONCLUSIONS
Amitriptyline produces a concentration-related impairment on road-tracking performance. Therapeutic monitoring of amitriptyline would be useful for predicting the difficulties involved while driving.
Iwamoto
Kunihiro
K
Department of Psychiatry, Nagoya University, Graduate School of Medicine, Aichi, Japan.
Kawamura
Yukiko
Y
Takahashi
Masahiro
M
Uchiyama
Yuji
Y
Ebe
Kazutoshi
K
Yoshida
Keizo
K
Iidaka
Tetsuya
T
Noda
Yukihiro
Y
Ozaki
Norio
N
D000328:Adult; D000639:Amitriptyline / Q000493:pharmacokinetics* / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics* / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D001334:Automobile Driving; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects*
D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline